Effect of Cyclic Stretch on Neuron Reorientation and Axon Outgrowth.

Effect of Cyclic Stretch on Neuron Reorientation and Axon Outgrowth.
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循环拉伸对神经元重新定向和轴突生长的影响

DOI:
10.3389/fbioe.2020.597867
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发表时间:
2020
影响因子:
5.7
通讯作者:
Qian J
Qian J
中科院分区:
工程技术2区
文献类型:
--
作者:
Lin J;Li X;Yin J;Qian J

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神经元的定向排列和生长是神经再生和神经系统功能恢复的关键步骤,神经元暴露在复杂的力学环境中,应力纤维和焦点粘连等亚细胞结构是关键的力学转导。在本文中,我们研究了周期性拉伸对神经元重新定向和轴突生长的影响,并设计了一种可行的拉伸装置来控制拉伸的幅度和频率。统计结果表明,神经元重新定向具有明显的频率和幅度依赖性,即当拉伸幅度和频率足够大时,神经元倾向于远离拉伸方向。另一方面,循环拉伸下的轴突延长与神经元不拉伸的参考情况非常接近。通过将细胞构型的演化与包括应力纤维、焦点粘连和微管在内的亚细胞结构的微观动力学联系起来,提出了一个机械力化学框架,得到了与实验观察相一致的理论预测。这项理论工作解释了神经元对周期性拉伸的机械反应,表明应力纤维产生的收缩力在神经元重新定向和轴突延长中都起着重要作用。本实验与理论研究相结合,可能在神经发育和神经元再生方面具有潜在的应用前景。
The directional alignment and outgrowth of neurons is a critical step of nerve regeneration and functional recovery of nerve systems, where neurons are exposed to a complex mechanical environment with subcellular structures such as stress fibers and focal adhesions acting as the key mechanical transducer. In this paper, we investigate the effects of cyclic stretch on neuron reorientation and axon outgrowth with a feasible stretching device that controls stretching amplitude and frequency. Statistical results indicate an evident frequency and amplitude dependence of neuron reorientation, that is, neurons tend to align away from stretch direction when stretching amplitude and frequency are large enough. On the other hand, axon elongation under cyclic stretch is very close to the reference case where neurons are not stretched. A mechanochemical framework is proposed by connecting the evolution of cellular configuration to the microscopic dynamics of subcellular structures, including stress fiber, focal adhesion, and microtubule, yielding theoretical predictions that are consistent with the experimental observations. The theoretical work provides an explanation of the neuron’s mechanical response to cyclic stretch, suggesting that the contraction force generated by stress fiber plays an essential role in both neuron reorientation and axon elongation. This combined experimental and theoretical study on stretch-induced neuron reorientation may have potential applications in neurodevelopment and neuron regeneration.
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